Nerve growth factor (NGF) and nerve growth factor receptors (NGFRs) play important roles in tissue remodeling during the would healing process of the skin, oral and paranasal mucosa, and cornea. The interactions between NGF and NGFRs are influenced by or interact with a number of molecules in the tissue remodeling process, in which key niche components are varieties of growth factors and their receptors, including NGF and NGFR. In addition to those interactions mentioned above, cell-cell contacts as well as cell-matrix interactions have also been considered to promote wound healing events. The present review focuses on the pathophysiological roles of NGF and NGFR in saliva and salivary glands, and in tear and lacrimal glands under inflammatory and tissue remodeling conditions, as well as their expression profiles in various kinds of cells including mast cells, macrophages, lymphocytes, and those involved in angiogenesis. Finally, we describe how the expression modes of NGF and NGFR regulate the peripheral nerve fiber growth and stimulate wound healing or tissue remodeling in the organs or tissues mentioned above as well as in pressure wounds and diabetic skin lesions. Based on these lines of evidence, we emphasize that NGF and NGFR could represent new and powerful regimens for treatment of tissue injuries.

Background: In addition to keratocystic odontogenic tumor (KCOT), orthokeratinized odontogenic cyst (OOC) has recently been recognized as a different jaw cyst entity whose lining epithelia are markedly keratinized. However, the odontogenic background of OOC remains still controversial. To clarify the difference in the lining epithelial natures of KCOT and OOC, we investigated differentiation modes for keratinization and neoplastic characteristics of these two cysts by immunohistochemistry for keratin subtypes and apoptosis-related proteins. Methods: Surgical specimens of KCOT (n = 20) and OOC (n = 15), as well as dentigerous cyst (DC, n = 15), which was used as a control, were examined by immunohistochemistry and western blotting for their expressions for cytokeratin (CK) 1, CK13, Bcl-2, and Bax. Immunohistochemical reactions were evaluated separately in two epithelial layers: upper spinous and basal. Results: Most of the spinous cells in the upper layer of KCOT and DC were CK13 positive (90-100%), while they were not as conspicuous in OOC (20%). In contrast, CK1 was positive in OOC (100%), while it was not positive in KCOT and DC. Basal layer cells in KCOT were positive for Bcl-2 (100%) but not for Bax (0%). Instead, they were not positive for Bcl-2 but positive Bax in OOC and DC. These immunohistochemical profiles in the three cystic lesions were confirmed by western blot analyses showing CK13 in KCOT and DC and CK1 in OOC. Conclusions: The CK expression modes were similar between KCOT and DC, indicating their odontogenic characteristics, which were not evident in OOC. The Bcl-2 positivity in KCOT suggested its neoplastic nature, though there was no neoplastic evidence in OOC and DC.

Background: Eosinophilic round bodies (ERBs) are composed of fragments of amino acid sequences of varying lengths, which represent a portion of exon 5 of amelogenin gene. ERBs have previously been shown to accumulate in the backs of rats subcutaneously injected with the product Emdogain®. In the present study, an oligopeptide with an amino acid sequence similar to this portion was artificially synthesized, and its effects were examined. Methods: The peptide solution was applied to periodontal defects created on the maxillae of rats. Sections from these tissues were histopathologically and immunohistochemically examined at 7 and 14 days after the start of the experiment. Results: In the experimental group, hard tissue had formed on the surface of exposed dentin, and both osteopontin and collagen type I (COLI) were localized around the hard tissue. The hard tissue was stained with periodic acid-Schiff (PAS) more deeply than was the dentin, and the fibers that were positive for COLI were vertically inserted in the rim of the newly-formed hard tissue. No hard tissue formation was found in the control group. Conclusion: These results suggest that synthetic oligopeptide administration can induc

Background: Oral cancers with sequential backgrounds have been increasing in number in recent years in Japan, although their disease entity is not always well defined. To characterize their clinicopathological nature, we compared oral cancers having sequential backgrounds with those lacking an apparent sequential history. Methods: From primary oral cancer cases filed in Niigata University Hospital, tongue cancer cases were selected and analyzed for their clinical factors (sex, age, location, TNM stages, local recurrences, and multiple occurrences), and for oral environmental factors (smoking and drinking habits, as well as the wearing of dentures or crown bridges). The histopathological characteristics were examined using surgical specimens. Results: Using samples from a 38-year period, 1970 to 2007, we were able to confirm 119 cases of squamous cell carcinoma of the tongue. Based on the clinicopathological analyses, we separated them into two categories: de novo type and sequential type. The latter was characterized by its superficial spread associated with precursor lesions, while the former appeared as an exophytic tumor mass with intrinsic growth and ulceration, without associations with a precursor lesion in the vicinity of the main cancer foci. There were 44 de novo types (28 males, 16 females, average age 54.0 years) and 75 sequential types (38 males, 37 females, 62.1 years). Clinically, there were no statistically significant differences in age, sex, location, local recurrence, multiple occurrence, and distant metastasis between the two types, although sequential types were found more frequently in older females. Tumor sizes of sequential types were smaller than those of de novo type (P<0.05), and they had obviously less cervical lymph node metastasis than did de novo types (P<0.001). In addition, smoking and drinking habits were not as prevalent among sequential type female patients as among de novo type patients (P<0.001). Conclusion: The findings indicated that two different disease categories of oral squamous cell carcinoma could be identified. The sequential type, a newly-recognized one, frequently arises in older female individuals who report no conventional risk factors, such as smoking and drinking. This type has the better prognosis. Clinical interventions should distinguish between the two types.